New Aminoglycoside May Be Approved In June

It may seem surprising, but Achaogen is developing a new aminogycoside for the treatment of multi-drug resistant bacteria, including carbopenem resistant bacteria.  Achaogen filed an NDA in Oct 2017. In May, an FDA Advisory Committee voted 15-0 to recommend approval of plazomicin for the treatment of complicated UTI, but voted against recommending approval of the drug for bacteremia (4-11 to approve).

Achaogen announced  that plazomicin was found to be non-inferior  to meropenem for complicated UTI in a 609 patient, Phase III, EPIC trial. The drug also demonstrated lower mortality and complication rate than colestin in Phase III, CARE trial that enrolled 69 patients with carbapenem-resistant enterobacteriaceae bacteremia that were receiving meropenem or tigecycline. The original study was to include a cohort of patients with hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP), but due to problems in recruiting patients, the bacteremia cohort was combined with the HABP/VABP.  With the lower patient population, no statistical analysis was possible.  

Current trial data display no significant safety concerns; no independent safety data are yet available. The most common ADR reported in trials are diarrhea, hypertension, headache, nausea, and vomiting. In a review the FDA concluded that transient nephrotoxicity was seen in trials. While the sample size of the bacteremia trial was too small to determine if there was less nephrotoxicity than colistin, there was a trend in that direction. There was no ototoxicity found in studies, but the FDA did not feel the evidence of definitive. 

Researchers at Hartford Hospital, examined the compatibility of plazomicin with 92 drugs in a simulated Y-site administration test. Plazomicin was compatible with 79 of the drugs (31 antibiotics) and incompatible with 13.

Plazomicin has a PDUFA date of June 25, so we will likely see the first new aminoglycoside in decades be approved.